大鼠脊髓腰节段神经元存活信号转导通路及凋亡调控因子增龄变化.docVIP

大鼠脊髓腰节段神经元存活信号转导通路及凋亡调控因子增龄变化 　 作者：李雅莉 赵宁 张丽 李林 【摘要】 目的 观察大鼠脊髓腰节段神经元存活信号转导通路中重要因子和调控凋亡相关因子的增龄变化及与老化的关系。方法 按月龄将雄性SD大鼠分为1、3、6、12、18、24月龄6组。应用免疫组织化学染色和Western印迹法观察增龄大鼠脊髓腰节段神经元存活信号转导通路中的转导因子PI3K、pp70S6K、磷酯化环腺苷酸应答元件结合蛋白(pCREB)及凋亡调控因子Bax和Bcl2的表达情况。结果 大鼠脊髓腰节段神经元pp70S6K和pCREB随增龄变化明显，1月龄时表达量较低，3月龄时有所增高，至6月龄、12月龄达高峰，24月龄时明显减低；而PI3K的变化不大。大鼠脊髓腰节段Bax表达随年龄增高逐渐增加，至24月龄表达量达高峰；Bcl2表达随年龄增加而逐渐降低，至24月龄时降至最低点。与6月龄（青年期）大鼠相比，24月龄（老年期）大鼠脊髓腰节段神经元pp70S6K、pCREB和Bcl2表达明显降低，Bax表达显著增高。结论 老年大鼠脊髓腰节段pp70S6K、pCREB和Bcl2的表达明显降低， Bax表达显著增多，提示脊髓老化与神经元存活信号转导通路和凋亡调控因子的变化有关。 【关键词】 脊髓；老化；神经元存活信号转导通路；细胞凋亡 【Abstract】 Objective To investigate the changes in neuronal survival signal transduction pathway and apoptosis regulating factors in the lumbar spinal cord of ageincreasing rats, and to evaluate their correlation with aging. Methods Male SD rats were divided into 1, 3, 6, 12, 18 and 24monthold groups according to their age. The expressions of important factors in neuronal survival signal transduction pathway (PI3K, pp70S6K, pCREB) and apoptosis regulating factors (Bax, Bcl2) in the lumbar spinal cord of rats were measured by immunohistochemistry and Western blot. Results The expressions of pp70S6K and pCREB in the lumbar spinal cord was lower in 1monthold rats, increased at the age of 3 months, reached the peak in 6 and 12monthold rats, and decreased to the lowest level at the age of 24 months; but PI3K did not show significant changes. The expression of BAX was increased with age increasing, and reached the peak at the age of 24 months. The content of Bcl2 was reduced with ageing, and dropped to the bottom in 24monthold rats. Compared with those in young rats (6 month old), the expressions of pp70S6K, pCREB and Bcl2 were decreased and the content of Bax was increased significantly in the lumbar spinal cord of aged rats (24 month old). Conclusions Aged rats show a decrease in the expressions of pp70S6K, pCREB and Bcl2, and an increase in the content of Bax in the spi